Epothilones are macrolide compounds having utility in the pharmaceutical field. For example, Epothilones A and B having the structures:
may be found to exert microtubule-stabilizing effects similar to paclitaxel (TAXOL®) and hence cytotoxic activity against rapidly proliferating cells, such as, tumor cells or other hyperproliferative cellular disease, see Hofle et al., Angew. Chem. Int. Ed. Engl. Vol. 35, No. 13/14, 1567-1569 (1996); WO 93/10121 published May 27, 1993; and WO 97/19086 published May 29, 1997.
Derivatives and analogs of Epothilones A and B have been synthesized and may be used to treat a variety of cancers and other abnormal proliferative diseases. Such analogs are disclosed in Hofle et al., Id.; Nicolaou et al., Angew Chem. Int. Ed. Engl., Vol. 36, No. 19, 2097-2103 (1997); and Su et al., Angew Chem. Int. Ed. Engl, Vol. 36, No. 19, 2093-2097 (1997).
Analogs of the epothilones that have been found to have advantageous activity are represented by formula I:
wherein the various symbols are as defined below. While these compounds possess significant therapeutic properties, they also present difficulties to those skilled in the art of pharmaceutical compounding, as a result of certain properties, as will be detailed hereinbelow. In accordance with the present invention, a formulation has been found whereby the epothilone analogs described above can be safely dispensed and administered via injection, without appreciable loss of potency.